FDA Arava® Warning

Federal regulators say they will require Sanofi-Aventis to place a black box warning on Arava after receiving a number of reports of liver damage on Arava, including at least 14 deaths since 2002.

What’s the problem?

The U.S. Food and Drug Administration (FDA) will now require the rheumatoid arthritis drug Arava (leflunomide) to include information on severe liver injury as part of its black box warning. Arava already carries a boxed warning that its use is contraindicated in pregnant women and women of child-bearing age who are not using a reliable contraception method. The new warning follows an FDA review of adverse events from the side effects of Arava reported between August 2002 and May 2009.

The FDA identified 49 cases of severe liver injury from Arava, including 14 fatalities. The most commonly reported problem was jaundice, but some patients reported encephalopathy and coagulopathy (blood clotting problems) as well. The FDA determined that those patients who had pre-existing liver problems and those taking other drugs that also increased the risk of liver injury were at the most risk.

The FDA is recommending that patients with pre-existing liver disease, or with elevated liver enzymes, not be given Arava. It also suggests that doctors monitor the liver enzymes of patients on Arava monthly for at least three months after they start the drug, and at least quarterly after the first three months. If liver enzymes climb to more than twice the upper limit of what’s considered within the normal range, the patient should be taken off Arava and should be given cholestryamine to speed up the drug’s removal from the body.